Maintenance Low Dose 5'-Azacitidine Post T Cell Depleted Allogeneic Stem Cell Transplantation for Patients With Myelodysplastic Syndrome and Acute Myelogenous Leukemia With High Risk for Post-Transplant Relapse

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01995578

Collaborator

(none)

Enrollment

Locations

Arm

107

Duration (Months)

4.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to learn if 5'-Azacitidine will help to lower the risk of the disease coming back after a stem cell transplant in patients with MDS and AML. This study will also be looking at the side effects of this medicine.

5'-Azacitidine is an FDA approved drug for treatment of MDS and AML, as well as patients whose disease came back after transplant, where it helped going into remission. It is unclear if 5'-Azacitidine can prevent the disease from coming back after transplant. This study will help show if getting 5'-Azacitidine soon after transplant can lower the risk of your disease coming back.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes (MDS) Acute Myelogenous Leukemia (AML)	Drug: low dose 5'-azacitidine	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Single Arm Phase II Trial of Maintenance Low Dose 5'-Azacitidine Post T Cell Depleted Allogeneic Stem Cell Transplantation for Patients With Myelodysplastic Syndrome and Acute Myelogenous Leukemia With High Risk for Post-Transplant Relapse

Study Start Date :

Dec 1, 2013

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Nov 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: low dose 5'-azacitidine This is a single arm phase II trial to assess the efficacy and confirm the safety of maintenance therapy with 5'-azacitadine compared to historical control after TCD allogeneic hematopoietic stem cell transplant for patients with MDS and AML who are at high risk of relapse.	Drug: low dose 5'-azacitidine 5'-azacitadine will be given at a low dose of 32mg/m2 S.C for 5 days every 28 days (a cycle). Dose de-escalation will be permitted for hematologic and non- hematologic toxicities. Patients will start taking the study drug between days 60-120 post TCD allogeneic hematopoietic stem cell transplant and up to a year post-transplant or until there is a toxicity that requires cessation of therapy. Therefore patients will get between 8-10 cycles. Patients who come off-study for reasons unrelated to toxicities before completing 4 cycles will be replaced Since most cases of relapse occur early post transplant, in the first year, this is the most appropriate time to intervene. Treatment will start as soon as possible.

Arm

Intervention/Treatment

Experimental: low dose 5'-azacitidine

This is a single arm phase II trial to assess the efficacy and confirm the safety of maintenance therapy with 5'-azacitadine compared to historical control after TCD allogeneic hematopoietic stem cell transplant for patients with MDS and AML who are at high risk of relapse.

Drug: low dose 5'-azacitidine

5'-azacitadine will be given at a low dose of 32mg/m2 S.C for 5 days every 28 days (a cycle). Dose de-escalation will be permitted for hematologic and non- hematologic toxicities. Patients will start taking the study drug between days 60-120 post TCD allogeneic hematopoietic stem cell transplant and up to a year post-transplant or until there is a toxicity that requires cessation of therapy. Therefore patients will get between 8-10 cycles. Patients who come off-study for reasons unrelated to toxicities before completing 4 cycles will be replaced Since most cases of relapse occur early post transplant, in the first year, this is the most appropriate time to intervene. Treatment will start as soon as possible.

Outcome Measures

Primary Outcome Measures

relapse rate [2 years]
Relapse of MDS or AML will be analyzed as to type and genetic origin of the leukemic cells. These will be defined by morphologic and/or cytogenetic criteria: an increasing number of blasts in the marrow over 5%, by presence of circulating blasts, or by presence of blasts in any extramedullary site as well as presence of previous cytogenetic abnormalities. Other studies assessing for MRD, FACS and FISH assays will be evaluated but would not be considered disease relapse if positive since they are experimental.

Secondary Outcome Measures

overall survival [2 years]
Kaplan-Meier methodology will be used to compare overall survival.
safety [2 years]
The safety will be described by tabulating the number of transfusions, frequencies of bleeding and serious infections, and the use of G-CSF support.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients who have undergone T cell depleted allogeneic hematopoietic stem cell transplantation at MSKCC for:

De novo myelodysplastic syndromes (MDS): IPSS-1 with poor risk cytogenetics or higher IPSS.
Acute myelogenous leukemia (AML) in first remission that required more than 1 cycle of treatment to achieve remission or with the following cytogenetic abnormalities: FLT3 mutation, deletion/monosomy of chromosome 5 or 7, MLL gene rearrangement, or more than or equal to 3 cytogenetics abnormalities. Also patients in second or greater remission.
Patients with Secondary MDS/AML.
Patients will be considered eligible for the study if after transplant they achieved hematologic (<5% blasts) and cytogenetic remission.
Patients will be eligible to enter the study between 60-120 days post transplant.
Age: pediatrics and adults patients - 1 year old-75 years old.
Karnofsky performance status >=60% for patients >16yo and Lansky performance status

=60% for patients ≤16yo

Stable blood counts (ANC>1000/uL, Hb>8gr/dL, Plt>50,000/ uL) not supported by transfusions.
Renal: Serum creatinine <1.5 ULN
Hepatic: <3xULN ALT and <1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
Cardiac: Adequate cardiac function measured by LVEF>50%. If asymptomatic, pretransplant echocardiogram is adequate. If symptomatic, echocardiogram needs to be repeated.
Each patient must be willing to participate as a research subject and must sign an informed consent form.

Exclusion Criteria:

Patients will be excluded from the trial if at time of enrollment:

Active uncontrolled bacterial, fungal or viral infection.
Evidence of uncontrolled graft-versus-host disease.
Pulmonary: new onset hypoxia
Known or suspected hypersensitivity to 5'-azacitadine or mannitol.
Evidence of residual disease either by increased blasts count (>5%) or persistence of previous known cytogenetics abnormalities.
Peripheral blood neutrophil chimerism: less than 95% donor.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering at Basking Ridge (Consent and Follow-up)	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Monmouth (Consent and Follow-up)	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen (Consent and Follow-up)	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Commack (Consent and Follow-up)	Commack	New York	United States	11725
5	Memorial Sloan Kettering Westchester (Consent and Follow-up)	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau (Consent and Follow-up)	Rockville Centre	New York	United States